Cholesterol homeostasis in human brain: evidence for an age-dependent flux of 24S-hydroxycholesterol from the brain into the circulation.

We have investigated whether side chain-hydroxylated cholesterol species are important for elimination of cholesterol from the brain. Plasma concentrations of 24-hydroxycholesterol (24-OH-Chol) in the internal jugular vein and the brachial artery in healthy volunteers were consistent with a net flux of this steroid from the brain into the circulation, corresponding to elimination of approximately 4 mg cholesterol during a 24-h period in adults. Results of experiments with rats exposed to 18O2 were also consistent with a flux of 24-OH-Chol from the brain into the circulation. No other oxysterol measured showed a similar behavior as 24-OH-Chol. These results and the finding that the concentration of 24-OH-Chol was 30- to 1500-fold higher in the brain than in any other organ except the adrenals indicate that the major part of 24-OH-Chol present in the circulation originates from the brain. Both the 24-OH-Chol present in the brain and in the circulation were the 24S-stereoisomer. In contrast to other oxysterols, levels of plasma 24-OH-Chol were found to be markedly dependent upon age. The ratio between 24-OH-Chol and cholesterol in plasma was approximately 5 times higher during the first decade of life than during the sixth decade. There was a high correlation between levels of 24-OH-Chol in plasma and cerebrospinal fluid. It is suggested that the flux of 24-OH-Chol from the brain is important for cholesterol homeostasis in this organ.

Noninvasive tests for arterial structure, function, and compliance: Do they identify risk or diagnose disease?

Background: Brachial artery reactivity (BAR), carotid intima-media thickness (IMT), and applanation tonometry for evaluation of total arterial compliance may provide information about preclinical vascular disease. We sought to determine whether these tests could be used to identify patients with coronary artery disease (CAD) without being influenced by their ability to identify those at risk ford CAD developing. Methods: We studied 100 patients and compared 3 groups: 35 patients with known CAD; 34 patients with symptoms and risk factors but no CAD identified by stress echocardiography (risk group); and 31 control subjects. BAR and IMT were measured using standard methods, and total arterial compliance was calculated by the pulse-pressure method from simultaneous radial applanation tonometry and pulsed wave Doppler of the left ventricular outflow. Ischemia was identified as a new or worsening wall-motion abnormality induced by stress. Results: In a comparison between the control subjects and patients either at risk for developing CAD or with CAD, the predictors of risk for CAD were: age (P = .01); smoking history (P = .002); hypercholesterolemia (P = .002); and hypertension (P = .004) (model R = 0.82; P = .0001). The independent predictors of CAD were: IMT (P = .001); BAR (P = .04); sex (P = .005); and hypertension (P = .005) (model R = 0.80; P = .0001). Conclusion: IMT, BAR, and traditional cardiovascular risk factors appear to identify patients at risk for CAD developing. However, only IMT was significantly different between patients at risk for developing CAD and those with overt CAD.

The relative importance of vascular structure and function in predicting cardiovascular events

OBJECTIVES We sought to assess the prognostic utility of brachial artery reactivity (BAR) in patients at risk of cardiovascular events. BACKGROUND Impaired flow-mediated vasodilation measured by BAR is a marker of endothelial dysfunction. Brachial artery reactivity is influenced by risk factors and is responsive to various pharmacological and other treatments. However, its prognostic importance is uncertain, especially relative to other predictors of outcome. METHODS A total of 444 patients were prospectively enrolled to undergo BAR and follow-up. These patients were at risk of cardiovascular events, based on the presence of risk factors or known or suspected cardiovascular disease. We took a full clinical history, performed BAR, and obtained carotid intima-media thickness (IMT) and left ventricular mass and ejection fraction. Patients were followed up for cardiovascular events and all-cause mortality. Multivariate Cox regression analysis was performed to assess the independent association of investigation variables on outcomes. RESULTS The patients exhibited abnormal BAR (5.2 +/- 6.1% [mean +/- SD]) but showed normal nitrate-mediated dilation (9.9 +/- 7.2%) and normal mean IMT (0.67 +/- 0.12 mm [average]). Forty-nine deaths occurred over the median follow-up period of 24 months (interquartile range 10 to 34). Patients in the lowest tertile group of BAR (<2%) had significantly more events than those in the combined group of highest and mid-tertiles (p = 0.029, log-rank test). However, mean IMT (rather than flow-mediated dilation) was the vascular factor independently associated with mortality, even in the subgroup (n = 271) with no coronary artery disease and low risk. CONCLUSIONS Brachial artery reactivity is lower in patients with events, but is not an independent predictor of cardiovascular outcomes in this cohort of patients. (C) 2004 by the American College of Cardiology Foundation.

No relationship between low-density lipoproteins and endothelial function in hemodialysis patients

Background: Relationships between low-density lipoprotein cholesterol and endothelial function in hemodialysis patients have yet to be investigated. Furthermore, current reporting of endothelial function data using flow-mediated dilatation has recognised limitations. The aims of the study were to determine the relationship between low-density lipoproteins and endothelial function in hemodialysis patients and to investigate the validity of determining the area under the curve for data collected during the flow-mediated dilatation technique. Methods: Brachial artery responses to reactive hyperemia (endothelial-dependent) and glyceryl trinitrate (endothelial-independent) were assessed in 19 hemodialysis patients using high-resolution ultrasound. Lipid profiles and other factors known to effect brachial artery reactivity were also measured prior to the flow-mediated dilatation technique. Results: There were no significant relationships between serum low-density lipoproteins and endothelial-dependent or -independent vasodilation using absolute change (mm), relative change (%), time to peak change (s) or area under the curve (mm(.)s). In hemodialysis patients with atherosclerosis, area under the curve analysis showed a significantly (p < 0.05) decreased endothelial-dependent response (mean +/- S.D.: 19.2 +/- 17.4) compared to non-atherosclerotic patients (42.3 +/- 28.6). However, when analysing these data using absolute change, relative change or time to peak dilatation, there were no significant differences between the two groups. Conclusions: In summary, there was no relationship between low-density lipoproteins and endothelial function in hemodialysis patients. In addition, area under the curve analysis of flow-mediated vasodilatation data may be a useful method of determining the temporal vascular response during the procedure. (c) 2004 Elsevier Ireland Ltd. All rights reserved.

Ocular and systemic markers for vascular function in those at risk of type 2 diabetes mellitus and cardiovascular disease

The devastating impact of Type 2 Diabetes Mellitus (T2DM) -related morbidity and mortality on global healthcare is escalating with higher prevalences of obesity, poor diet, and sedentary lifestyles. Therefore, the clinical need for early diagnosis and prevention in groups of high-risk individuals is necessary. The purpose of this thesis was to investigate the use of surrogate markers, namely retinal vascular function, to determine future vascular endothelial dysfunction, atherosclerosis, large vessel disease and cardiovascular risk in certain groups. This namely covered normoglycaemic and normotensive South Asians (SAs), those with Impaired-Glucose Tolerance (IGT) and individuals with a familial history (FH) of T2DM. Additionally the effect of overweight and obesity was studied. The techniques and modified protocols adopted for this thesis involved the investigation of endothelial function by means of vascular reactivity at the ocular and systemic level. Furthermore, the relationships between retinal and systemic function with circulating markers for endothelial cell function and cardiovascular risk markers were explored. The principal studies and findings of the research were: Vascular Function in Normoglycaemic Individuals with and without a FH of T2DM WE FH individuals exhibited higher levels of total cholesterol levels that correlated well with the retinal arterial dilation amplitude to flicker light stimulus. However this did not extend to noticeable differences in markers for endothelial cell damage and impaired retinal and systemic function. Vascular Function in Normoglycaemic South-Asians vs. White-Europeans without a FH and Vascular Disturbances Compared to healthy WEs (normo -glycaemic and -tensive), SA participants exhibited levels of dyslipidaemia and a state of oxidative stress that extended to impaired vascular function as detected by reduced brachial artery flow-mediated dilation, slower retinal arterial vessel dilation reaction times (Appendix 3) and steeper constriction profiles. Furthermore, gender sub-group analysis presented in a sub-chapter shows that SA males demonstrated 24-hour systemic blood pressure (BP) and heart rate variability (HRV) abnormalities and heightened cardiovascular disease (CVD) risk. Vascular Function in Individuals Newly Diagnosed with IGT as compared to Normoglycaemic Healthy Controls Newly-diagnosed WE and SA IGT patients showed a greater risk for CVD and T2DM progression by means of 24-hour BP abnormalities, dyslipidaemia, increased carotid artery intimal-media thickness (c-IMT), Framingham scores and cholesterol ratios. Additionally, pre-clinical markers for oxidative stress and endothelial dysfunction, as evident by significantly lower levels of plasma glutathione and increased levels of von-Willebrand factor in IGT individuals, extended to impaired vascular systemic and retinal function compared to normal controls. This originally shows retinal, systemic and biochemical disturbances in newly-diagnosed IGT not previously reported before. Vascular Function in Normal, Overweight and Obese Individuals of SA and WE Ethnicity In addition to the intended study chapters, the thesis also investigated the influence of obesity and overweight on vascular function. Most importantly, it was found for the first time that compared to lean individuals it was overweight and not obese individuals that exhibited signs of vascular systemic and ocular dysfunction that was evident alongside markers of atherosclerosis, CVD risk and endothelial damage.

Abnormal retinal vascular reactivity in individuals with impaired glucose tolerance:a preliminary study

To investigate the relationship between vascular function parameters measured at the retinal and systemic level and known markers for cardiovascular risk in patients with impaired glucose tolerance (IGT). Sixty age- and gender- matched White-European adults (30 IGT and 30 normal glucose tolerance -NGT) were recruited for the study. Fasting plasma glucose, lipids and 24-hour blood pressure (BP) was measured in all subjects. Systemic vascular and endothelial function was assessed using carotid-artery intimal media thickness (cIMT) and flow mediated dilation (FMD). Retinal vascular reactivity was assessed by the Dynamic Retinal Vessel Analyser (DVA). Additionally, blood glutathione (GSH, GSSG and tGSH) and plasma von-Willebrand (vWF) factor levels were also measured. Individuals with IGT demonstrated higher BP values (p<0.001), fasting TG and TG:HDL ratios (p<0.001) than NGT subjects. Furthermore, Total:HDL-C ratios and Framingham scores were raised (p=0.010 and p<0.001 respectively). Blood glutathione levels (GSH, GSSG and tGSH) were lower (p<0.001, p=0.039 and p<0.001 respectively) while plasma vWF was increased (p=0.014) in IGT subjects compared to controls. IGT individuals also demonstrated higher IMT in right and left carotid arteries (p=0.017 and p=0.005, respectively) alongside larger brachial artery diameter (p=0.015), lower FMD% (p=0.026) and GTN induced dilation (GID) (p=0.012) than healthy controls. At the retinal arterial level, the IGT subjects showed higher baseline fluctuations (BDF) (p=0.026), longer reaction time (RT) (p=0.032) and reduced baseline-corrected flicker response (bFR) (p=0.045). In IGT subjects retinal BDF correlated with and Total:HDL (p= 0.003) and HDL-C (p= 0.004). Arterial RT also correlated with FMD (p=0.017) in IGT but not NGT subjects. In IGT individuals there is a relationship between macro- and microvascular function, as well as a direct correlation between the observed retinal microcirculatory changes and established plasma markers for CVD. Multifactorial preventive interventions to decrease vascular risk in these individuals should be considered.

Ocular and systemic endothelial function in the off spring of diabetics:a pilot study

Purpose To investigate ocular and systemic correlates of endothelial function in the normoglycaemic offspring of Type 2 Diabetics (T2DM). Methods Healthy participants aged between 25-65 with (n=30) and without (n=39) a family history were recruited. Retinal vessel reactivity was assessed by using the Retinal Vessel Analyser (RVA, Imedos GmBH). In addition, systemic endothelial function was assessed by using the flow mediated dilation (FMD) technique. Results Parametric testing showed no significant differences in anthropometric, blood assay or ocular and systemic function between both groups (p>0.05). The average maximum dilation in the measured retinal artery correlated significantly with the maximum dilation of the measured brachial artery (p=0.002 R=0.55) in healthy controls; however, this was not true for subjects with family history of T2DM. Conclusion Subjects with family history of T2DM show possibly early signs of endothelial dysfunction that, in certain conditions, could contribute to the higher risk of this group of developing similar pathology to their parents.

Does estrogen fluctuation throughout the menstrual cycle impact flow-mediated dilation during exercise in healthy premenopausal women?

The endothelium is the inner most layer of cells that lines all arteries. A primary function of endothelial cells is to regulate responses to increased blood flow and the resulting frictional forces or shear stress by producing factors such as nitric oxide that mediate arterial dilation (flow mediated dilation (FMD)). Menstrual cycle variations in estrogen (E2) have been shown to influence brachial artery (BA) FMD in response to transient increases in shear stress brought about by the release of a brief forearm occlusion (reactive hyperemia (RH)). FMD can also be assessed in response to a sustained shear stress stimulus such as that created with handgrip exercise (HGEX), and studies have shown that RH- and HGEX stimulated FMD provide unique information regarding endothelial function. However, the impact of menstrual phase on HGEX-FMD is unknown. Therefore, the purpose of this study was to determine the impact of cyclical changes in E2 levels on HGEX-FMD over two discrete phases of the menstrual cycle. FMD was assessed via ultrasound. 12 subjects (21 ± 2yrs) completed two experimental visits: (1) low estrogen phase (early follicular) and (2) High estrogen phase (late follicular). In each visit both RH- and HGEX-FMD (6 min handgrip exercise) were assessed. Results are mean ± SD. E2 increased from the low to the high estrogen phase of the menstrual cycle (low: 34 ± 8, high: 161 ± 113pg/mL, p = 0.004). There was no change in mean FMD between phases (RH-FMD: 7.7 ± 4.3% vs. 6.4 ± 3.1%, p = 0.139; HGEX-FMD: 4.8 ± 2.8% vs. 4.8 ± 2.3%, p = 0.979). The observation that both RH- and HGEX-FMD did not differ between phases indicates that menstrual cycle fluctuations in estrogen may not universally impact endothelial function in young, healthy premenopausal women. Further research is needed to improve our understanding of the mechanisms that underlie variability in the impact of menstrual phase on both transient and sustained FMD responses.

Common dyslipidemias, high lipoprotein(a) concentrations and endothelial function in the children of the STRIP study families

Extreme lipid values predisposing on illnesses are dyslipidemias. Dyslipidemias evolve in early childhood, but their significance or persistency is not well known. Common dyslipidemias may aggregate in the same families. This thesis is a part of the longitudinal randomized Special Turku coronary Risk factor Intervention Project STRIP, in which 1054 families with six months old children were randomized to a control or to an intervention group. The family lipid data from the first 11 years was used. Fasting samples at the age of five years defined the lipid phenotypes. The dyslipidemias coexisting in the parent and the child were studied. At the age of 11 years 402 children participated artery ultrasound studies. The significance of the childhood dyslipidemias and lipoprotein(a) concentration on endothelial function was evaluated with the flow mediated arterial dilatation test. Frequently elevated non-HDL cholesterol concentration from one to seven-year-old children associated to similar parental dyslipidemia that improved the predictive value of the childhood sample. The familial combinations were hypercholesterolemia (2.3%), hypertriglyceridemia (2.0%), familial combined hyperlipidemia (1.8%), and isolated low HDL-cholesterol concentration (1.4%). Combined hyperlipidemia in a parent predicted most frequently the child’s hyperlipidemia. High lipoprotein(a) concentration aggregated in some families and associated to childhood attenuated brachial artery dilatation. Hypercholesterolemia and high lipoprotein(a) concentration at five years of age predicted attenuated dilatation. This study demonstrated that parental dyslipidemias and high lipoprotein(a) concentration help to find early childhood dyslipidemias. The association of hypercholesterolemia and lipoprotein(a) concentration with endothelial function emphasizes the importance of the early recognition of the dyslipidemias.

Función endotelial y lipemia postprandial en adultos normolipídicos: Efecto del estado nutricional

El objetivo del presente estudio fue cuantificar la contribución del sobrepeso en la magnitud de la lipemia posprandial en sujetos normolipídicos. Se incluyeron 33 adultos normolipídicos en dos grupos (n=20, sobrepeso y (n=13 eutróficos, 66% hombres, edad media 31,2±7,6 años). Se midió la vasodilatación mediada por flujo (VMF), la velocidad de onda de pulso (VOP), el perfil lipídico, el cociente Log TG/c-HDL, la glucosa y presión arterial tras una ingesta estándar con alto contenido de grasa (79% Kcal/grasa). Se calculó, el Z-score de riesgo cardiovascular a partir de la suma de los residuos tipificados (Z) de las variables de riesgo cardiovascular. El estado de lipemia posprandial se midió en ayuno (0 min) y a los (60, 120, 180, y 240 min) posprandiales. El valor basal de la VMF y la VOP fue de 6,9±5,9% y 7.0±0.8 m/s, respectivamente. Se identificó que la lipemia posprandial reducía la WMF en 19,2% a los 60 min (5,9±1,5%) y a los 240 min (3,7±1,2%) (p<0,04), respectivamente. Este hallazgo se acompañó con un aumento en la VOP (p<0,05). Al dividir los sujetos en dos grupos según el IMC, los participantes en sobrepeso muestran cifras más elevadas en el Z-score de riesgo cardiovascular, la VOP, el Log TG/c-HDL y el Δ-VOP, (p<0,001). En conclusión los sujetos clasificados en sobrepeso muestran un perfil cardiometabolico asociado con un mayor riesgo cardiovascular.

Extrinsic compression of popliteal artery in asymptomatic athlete and non-athlete individuals - A comparative study using duplex scan (color duplex sonography)

Aim. Extrinsic compression of the popliteal artery and absence of surrounding anatomical abnormalities characterize the functional popliteal artery entrapment syndrome (PAES). The diagnosis is confirmed to individuals who have typical symptoms of popliteal entrapment and occlusion or important stenosis of the popliteal artery with color duplex sonography (CDS), magnetic resonance imaging (MRI) or arteriography during active plantar flexion-extension maneuvers. However, variable result findings in normal asymptomatic subjects have raised doubts as to the validity of these tests. The purpose of this study was to compare the frequency of popliteal artery compression in 2 groups of asymptomatic subjects, athletes and non-athletes.Methods. Forty-two individuals were studied. Twenty-one subjects were indoor soccer players, and 21 were sedentary individuals. Physical activity was evaluated through questionnaires, anthropometric measurements, and cardiopulmonary exercise test. Evaluation of popliteal artery compression was performed in lower limbs with CDS, ankle-brachial index (ABI) measurements and continuous wave Doppler of the posterior tibial artery.Results. The athletes studied fulfilled the criteria of high level of physical activity whereas sedentary subjects met the criteria of low level of activity. Popliteal artery compression was observed with CDS in 6 (14.2%) studied subjects; 2 of whom (4.7%) were athletes and 4 (9.5%) were non-athletes. This difference was not statistically significant (p=0.21). Doppler of the tibial arteries and ABI measurements gave good specificity and sensibility in the identification of popliteal artery compression.Conclusion. The frequency of popliteal artery compression during maneuvers in normal subjects was 14.2% irrespective of whether or not they performed regular physical activities. Both Doppler and ABI showed good agreement with CDS and should be considered in screening popliteal arteries in individuals suspected of PAES.

Ankle-Brachial Index: A Simple Way to Predict Mortality among Patients on Hemodialysis - A Prospective Study

Background: Ankle-brachial index (ABI) can access peripheral artery disease and predict mortality in prevalent patients on hemodialysis. However, ABI has not yet been tested in incident patients, who present significant mortality. Typically, ABI is measured by Doppler, which is not always available, limiting its use in most patients. We therefore hypothesized that ABI, evaluated by a simplified method, can predict mortality in an incident hemodialysis population. Methodology/Principal Findings: We studied 119 patients with ESRD who had started hemodialysis three times weekly. ABI was calculated by using two oscillometric blood pressure devices simultaneously. Patients were followed until death or the end of the study. ABI was categorized in two groups normal (0.9-1.3) or abnormal (<0.9 and >1.3). There were 33 deaths during a median follow-up of 12 months (from 3 to 24 months). Age (1 year) (hazard of ratio, 1.026; p = 0.014) and ABI abnormal (hazard ratio, 3.664; p = 0.001) were independently related to mortality in a multiple regression analysis. Conclusions: An easy and inexpensive technique to measure ABI was tested and showed to be significant in predicting mortality. Both low and high ABI were associated to mortality in incident patients on hemodialysis. This technique allows nephrologists to identify high-risk patients and gives the opportunity of early intervention that could alter the natural progression of this population.

Endovascular treatment of popliteal artery aneurysms: a single-center experience

PURPOSE: To evaluate the use of covered stent-grafts in the endovascular treatment (ET) of popliteal artery aneurysms (PAAs). MATERIALS AND METHODS: A retrospective analysis was conducted over a period of 52 months in 18 consecutive patients (17 men; mean age +/- SD, 70 years +/- 11) undergoing ET of PAAs with the Viabahn endograft in a single center. Patient symptoms, aneurysm characteristics, technical outcomes, complications, and follow-up were assessed. RESULTS: Aneurysm diameters ranged from 12 to 51 mm with a mean of 30 mm (+/-11). Thirteen aneurysms (72.2%) were partially thrombosed and 12 patients (66.6%) had symptoms of lower limb ischemia at presentation (11 chronic and one acute). The technical success rate was 94%. Intraprocedural emboli and endoleak occurred in one and two patients, respectively. Fourteen patients were available for follow-up after successful treatment, with a mean follow-up time of 15 months (range, 7-37 months). All stent-grafts were patent after 1 month, with no mortality or limb loss. The primary patency rate with complete exclusion of the aneurysm at 6 months was 86%. Pre- and postprocedural noninvasive arterial studies were available in 10 patients, demonstrating improvement of the ankle-brachial index from 0.96 +/- 0.41 to 1.17 +/- 0.18, respectively (P = .06). CONCLUSIONS: Endovascular stent-graft repair of PAAs is a feasible treatment option. However, further follow-up studies regarding the durability of results are required.

Vascular hospitalization rates and costs in patients with peripheral artery disease in the United States

BACKGROUND: Peripheral artery disease (PAD) is common and imposes a high risk of major systemic and limb ischemic events. The REduction of Atherothrombosis for Continued Health (REACH) Registry is an international prospective registry of patients at risk of atherothrombosis caused by established arterial disease or the presence of 3 atherothrombotic risk factors. METHODS AND RESULTS: We compared the 2-year rates of vascular-related hospitalizations and associated costs in US patients with established PAD across patient subgroups. Symptomatic PAD at enrollment was identified on the basis of current intermittent claudication with an ankle-brachial index (ABI) <0.90 or a history of lower-limb revascularization or amputation. Asymptomatic PAD was diagnosed on the basis of an enrollment ABI <0.90 in the absence of symptoms. Overall, 25 763 of the total 68 236-patient REACH cohort were enrolled from US sites; 2396 (9.3%) had symptomatic and 213 (0.8%) had asymptomatic PAD at baseline. One- and cumulative 2-year follow-up data were available for 2137 (82%) and 1677 (64%) of US REACH patients with either symptomatic or asymptomatic PAD, respectively. At 2 years, mean cumulative hospitalization costs, per patient, were $7445, $7000, $10 430, and $11 693 for patients with asymptomatic PAD, a history of claudication, lower-limb amputation, and revascularization, respectively (P=0.007). A history of peripheral intervention (lower-limb revascularization or amputation) was associated with higher rates of subsequent procedures at both 1 and 2 years. CONCLUSIONS: The economic burden of PAD is high. Recurring hospitalizations and repeat revascularization procedures suggest that neither patients, physicians, nor healthcare systems should assume that a first admission for a lower-extremity PAD procedure serves as a permanent resolution of this costly and debilitating condition.

A modified calculation of ankle-brachial pressure index is far more sensitive in the detection of peripheral arterial disease

BACKGROUND: Ankle-brachial pressure index (ABI) is a simple, inexpensive, and useful tool in the detection of peripheral arterial occlusive disease (PAD). The current guidelines published by the American Heart Association define ABI as the quotient of the higher of the systolic blood pressures (SBPs) of the two ankle arteries of that limb (either the anterior tibial artery or the posterior tibial artery) and the higher of the two brachial SBPs of the upper limbs. We hypothesized that considering the lower of the two ankle arterial SBPs of a side as the numerator and the higher of the brachial SBPs as the denominator would increase its diagnostic yield. METHODS: The former method of eliciting ABI was termed as high ankle pressure (HAP) and the latter low ankle pressure (LAP). ABI was assessed in 216 subjects and calculated according to the HAP and the LAP method. ABI findings were confirmed by arterial duplex ultrasonography. A significant arterial stenosis was assumed if ABI was <0.9. RESULTS: LAP had a sensitivity of 0.89 and a specificity of 0.93. The HAP method had a sensitivity of 0.68 and a specificity of 0.99. McNemar's test to compare the results of both methods demonstrated a two-tailed P < .0001, indicating a highly significant difference between both measurement methods. CONCLUSIONS: LAP is the superior method of calculating ABI to identify PAD. This result is of great interest for epidemiologic studies applying ABI measurements to detect PAD and assessing patients' cardiovascular risk.